The bi-directional communication between the central nervous system and other organ systems is a critical event for the maintenance of mental and physical health. An example of such a communication is the interaction between the neuroendocrine and immune systems. Evidence for this psychoneuro-immune interaction is derived from studies showing that neuroendocrine hormones regulate in vivo and in vitro immune function. Neuroendocrine hormones are thought to be in involved in immunological abnormalities associated with; drug addiction, post traumatic stress syndrome, and more recently acquired immunodeficiency syndrome (AIDS) Acute stress is known to activate corticotropin-releasing factor which induces the anterior lobe of the pituitary gland to release opioid peptide hormones in quantities sufficient to suppress humoral and cell- mediated immunity in both man and animals. In addition to neuroendocrine production of opioid peptides, cells of the immune system are reported to synthesize opioid-like peptides. Thus, neuroendocrine production, the potential de novo synthesis of opioid peptides by cells of the immune system, and their known regulatory action within the immune microenvironment suggest that neuroendocrine peptide hormones may form part of an autocrine/paracrine regulatory network for the control of lymphocyte activation. Immunosuppression associated with immunodeficiency states may be due in part to aberrant activation of this immunoregulatory circuit. The major hypothesis of this proposal is that opioid or opioid-like peptide hormones are involved in the suppression of B lymphocyte differentiation to antibody synthesis. These peptide hormones may suppress antibody synthesis by acting directly on B lymphocytes and/or indirectly by influencing cytokine synthesis/action by monocytes and T lymphocytes. Major questions to be asked are: 1. What is specificity of opioid-receptor interactions in the suppression of antibody synthesis? Opioid specific receptor agonists and antagonists (delta, eta, and kappa) will be assessed for immunoregulatory activity. 2. Do human PBMC (Mo,T, and B cells) express receptors for opioid peptides? The expression of eta, delta, and kappa-specific receptors on stimulated and unstimulated cells will be assessed. 3. What are the mechanisms by which opioid peptides suppress antibody synthesis? Studies will be conducted to determine if opioid peptides suppress: a) the synthesis/action of accessory cytokines; b) synthesis of a specific IgG subclass; c) IgG synthesis at the level of transcription or translation.